A Study to Test Whether ZS (Sodium Zirconium Cyclosilicate) Can Reduce the Incidence of Increased Blood Potassium Levels Among Dialized Patients.

Hyperkalemia Clinical Trial

— DIALIZE  

Official title:

A Phase 3b, Multicenter, Prospective, Randomized, Double Blind, Placebocontrolled Study to Reduce Incidence of Pre-dialysis Hyperkalemia With Sodium Zirconium Cyclosilicate (DIALIZE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03303521
• Other study ID #: D9480C00006
• Secondary ID: 2017-003029-14
• Status: Completed
• Phase: Phase 3
• Start date: December 14, 2017
• Est. completion date: November 7, 2018

Study information

• Verified date: February 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of ZS in the treatment of hyperkalemia in patients on hemodialysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: November 7, 2018
• Est. primary completion date: November 7, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures

2. Female or male aged = 18 years at screening Visit 1. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.

3. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage renal disease (ESRD) for at least 3 months before randomization.

4. Patients must have hemodialysis access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study.

5. Pre-dialysis serum K >5.4 mmol/L after long inter-dialytic interval and >5.0 mmol/L after one short inter-dialytic interval during screening (as assessed by central lab).

6. Prescribed dialysate K concentration = 3 mmol/L during screening

7. Sustained Qb =200 ml/min and spKt/V =1.2 (or URR = 63) on stable hemodialysis/hemodiafltration prescription during screening with prescription (time, dialyzer, blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration) expected to remain unchanged during study

8. Heparin dose (if used) must be stable during screening and expected to be stable during the study

9. Subjects must be receiving dietary counseling appropriate for ESRD patients treated with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary potassium restriction.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca, including ZS Pharma staff and/or staff at the study site)

2. Hemoglobin <9 g/dL on screening (as assessed on Visit 1)

3. Lack of compliance with hemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required)

4. Patients treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7 days before screening or anticipated in requiring any of these agents during the study

5. Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to randomization

6. Laboratory diagnosis of hypokalemia (K < 3.5 mmol/L), hypocalcemia (Ca < 8.2 mg/dL; for Japan hypocalcemia is defined as albumin-corrected Ca < 8.0 mg/dL), hypomagnesemia (Mg < 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization

7. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).

8. Severe leukocytosis (>20× 10^9/L) or thrombocytosis (=450 × 10^9/L) during screening

9. Polycythemia (Hb >14 g/dL) during screening

10. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization

11. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug

12. Patients unable to take oral ZS drug mix

13. Scheduled date for living donor kidney transplant

14. Patients with a life expectancy of less than 6 months

15. Female patients who are pregnant or breastfeeding

16. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.

17. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof

18. Participation in another clinical study with an investigational product during the last 1 month before screening

19. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation

20. Presence of cardiac arrhythmias or conduction defects that require immediate treatment

21. History of alcohol or drug abuse within 2 years prior to randomization

22. Previous randomization in the present study

Related Conditions & MeSH terms

• Hyperkalemia

Intervention

Drug:
• Placebo
Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) . Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.
• Sodium Zirconium Cyclosilicate (ZS)
Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) . Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.

Locations

Country	Name	City	State
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Miyagi-gun
Japan	Research Site	Nagano-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Ora-gun
Japan	Research Site	Osaka-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sashima-gun
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Toride-shi
Japan	Research Site	Tsukuba-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Yachiyo-shi
Japan	Research Site	Yokosuka-shi
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Kolomna
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Podolsk
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St-Petersburg
Russian Federation	Research Site	Yaroslavl
Russian Federation	Research Site	Yekaterinburg
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Hull
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Swansea
United Kingdom	Research Site	York
United States	Research Site	Bronx	New York
United States	Research Site	East Providence	Rhode Island
United States	Research Site	El Paso	Texas
United States	Research Site	Fresh Meadows	New York
United States	Research Site	Great Neck	New York
United States	Research Site	Houston	Texas
United States	Research Site	Kansas City	Missouri
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Ontario	California
United States	Research Site	Paterson	New Jersey
United States	Research Site	Ridgewood	New York
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Dimas	California
United States	Research Site	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Japan,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Responders	A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval and did not receive rescue therapy. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.	Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
Primary	Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data	The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a "last observation carried forward" (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.	Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
Secondary	Percentage of Patients Needing Rescue Therapy	Patients requiring any urgent intervention consistent with local practice patterns to reduce serum potassium (S-K) including insulin/glucose, beta-adrenergic agonists, sodium bicarbonate, K binders or any form of renal replacement therapy.	An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.

External Links

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•   D9480C00006 SAP redacted